review article flushing and locking of venous catheters...

Review ArticleFlushing and Locking of Venous Catheters:Available Evidence and Evidence Deficit

Godelieve Alice Goossens1,2

1Nursing Centre of Excellence, University Hospitals Leuven, 3000 Leuven, Belgium2Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium

Correspondence should be addressed to Godelieve Alice Goossens; [email protected]

Received 12 November 2014; Accepted 24 February 2015

Academic Editor: Lisa Dougherty

Copyright © 2015 Godelieve Alice Goossens. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Flushing and locking of intravenous catheters are thought to be essential in the prevention of occlusion. The clinical sign of anocclusion is catheter malfunction and flushing is strongly recommended to ensure a well-functioning catheter. Therefore fluiddynamics, flushing techniques, and sufficient flushing volumes are important matters in adequate flushing in all catheter types. Ifa catheter is not in use, it is locked. For years, it has been thought that the catheter has to be filled with an anticoagulant to preventcatheter occlusion. Heparin has played a key role in locking venous catheters. However, the high number of risks associated withheparin forces us to look for alternatives. A long time ago, 0.9% sodium chloride was already introduced as locking solution inperipheral cannulas.More recently, a 0.9% sodium chloride lock has also been investigated in other types of catheters.Thrombolyticagents have also been studied as a locking solution because their antithrombotic effect was suggested as superior to heparin. Othercatheter lock solutions focus on the anti-infective properties of the locks such as antibiotics and chelating agents. Still, the mosteffective locking solution will depend on the catheter type and the patient’s condition.

1. Introduction

Flushing and locking have been strongly associated withthe prevention of catheter occlusion. The causes of catheterocclusion might be thrombotic, related to drug or par-enteral nutrition (PN) precipitates or mechanical. Throm-botic obstruction is caused by an intraluminal clot or acatheter tip thrombus. Precipitates might be formed by drugmixtures with an extreme pH, calcium phosphate crystals,or lipid deposits. Examples of mechanical obstruction aresleeve formation resulting in partial or total embedding ofthe catheter tip, a catheter tip abutting the vein wall, a pinchoff, a kinked or twisted catheter or tubing, tight sutures,or an incorrect Huber needle placement [1]. However thesemechanical occlusions are extraluminal causes of obstruc-tion. Flushing and locking maneuvers will not impact thesetypes of occlusion. On the contrary flushing and lockingare strongly associated with intraluminal occlusion followingbuild-up of deposits of fibrin and/or infusion fluids (likePN and dextrose) or a mixture of incompatible medicationsand solutions (Figures 1 and 2). Adequate flushing and

locking might also eliminate all potential nesting material formicroorganisms and thus also reduce the risk of catheter-related bloodstream infection (CRBSI) [2].

The aim of this paper is to clarify issues related to flushingand locking and to describe the available evidence relatingto the benefits of interventions in relation to occlusion. Alltypes of intravenous (IV) catheters are considered apartfrom apheresis and haemodialysis catheters and catheters inneonates due to the specific context of these devices.

2. Definition

In this context of rinsing the catheter, flushing of an IVcatheter is defined as a manual injection of 0.9% sodiumchloride or so called normal saline (NS) in order to cleanthe catheter. Locking is defined as the injection of a limitedvolume of a liquid following the catheter flush, for the periodof time when the catheter is not used, to prevent intraluminalclot formation and/or catheter colonization. Traditionally, ananticoagulant, such as diluted heparin, is used. Generally,flushing and locking are described ambiguously in guidelines

Hindawi Publishing CorporationNursing Research and PracticeVolume 2015, Article ID 985686, 12 pageshttp://dx.doi.org/10.1155/2015/985686

2 Nursing Research and Practice

Figure 1: Visible adhesions to the catheter wall.

Figure 2: Build-up of deposits of fibrin and/or infusion fluidsand/or drug precipitates.

and in the scientific literature which leads to confusionand misunderstanding. Moreover, flushing and locking areterms that are mutually exchanged [3–5]. The clinical signof occlusion is malfunction. Catheter malfunction is anycondition where, at least, injection or aspiration is no longereasy but has become difficult or impossible [6].

3. Flushing

3.1. Flushing Technique. Important aspects related to flushingare syringe diameter and injection flow dynamics. Tradition-ally, syringes with at least a diameter of 10mL are recom-mended for long-term central venous catheters. However,this issue arises only when force applied meets resistance.Flushing with a small syringe diameter or with high forceapplied to the plunger in cases of resistance increases therisk of catheter damage [7]. This is particularly true insilicone rubber catheters like tunnelled catheters which havea lowermaterial strength than polyurethane ones [8]. In thesetypes of catheters, weak spots originate when catheters areunintendedly stretched, especially in children. Subsequently,even an injection with a 10mL-diameter syringe may resultin a catheter rupture. In contrast, most peripherally insertedcentral catheters (PICCs) are made of a polyurethane sort ofmaterial and some are even approved for the high pressureof CT-power injection. Also, almost all totally implantablevenous access devices (TIVADs) or so called ports, in themarketplace, are power-injectable nowadays [9]. The strictneed to use only a minimum of 10mL-diameter syringes isredundant if these catheters and portsmaywithstand the highpressure of power injection.

The dynamic of the injection flow plays a pivotal role inadequate flushing. Vigier and colleagues showed in a qualita-tive in vitro study that flushing with an unsteady flow resultedin a significant reduction of the time scale of deadhesionof solid deposits compared to flushing with a laminar flow[10]. This research confirms the promoted practice of usinga so-called push-pause, pulsatile, or turbulent technique toenhance the rinsing effect in the catheter. Furthermore, basedon physics, not only the flow type but also the time intervalbetween two boluses is critical for efficient flushing. Indeed,Guiffant and colleagues filled a catheter lumen with a proteinbased liquid albumin in a laboratory setting. Ten mL of NSwas injected under two experimental conditions for catheterflushing, a laminar, and a pulsed flow. They measured theamount of recovered albumin from the lumen of the testeddevices. They found that intermittent flushes of 10 times onemL boluses with a time interval of 0.4 s between two boluseswas more efficient to rinse the catheter than shorter or longerpauses between two boluses. A continuous low flow infusion(500mL/24 h) was the less efficient [11]. Therefore, followingIV therapy, even after a continuous infusion of a 1000mL ofNS, a manual flush of 10mL is recommended. No RCT wasfoundwhich investigated the effectiveness of this intermittentflush versus a laminar injection flow technique.

3.2. Flushing Volume. An adequate flush volume is needed tobe able to remove debris and fibrin deposits in the catheterand port reservoir. Recommendations state the following:“use at least twice the volume of the catheter and add-ondevices” [3], and then the controversial words follow, “usually5–10mL” [4]. It is clear that 5–10mL is a much higher volumethan twice the catheter volume. However, especially in longcatheters such as PICCs and tunnelled catheters a largervolume than 5mL might be necessary to rinse the catheter.This is also the case in TIVADs because TIVADs consist ofa catheter and a port reservoir. The reservoir has a deadspace and a larger inner volume than a standard catheter.Adherence of lipid, fibrin, and other drug deposits to thereservoir wall may result in colonization of microorganismsand subsequently in CRBSI. Therefore in TIVADs, culturingthe reservoir is more sensitive than the catheter tip if port-related infection is suspected [12, 13]. Furthermore, inade-quate flushing might result in debris accumulation in thereservoir, so called sludge [14]. Clearing the chamber requiresa sufficient flushing volumewhichmay vary depending on theflow rate and the port type [15]. Ten mL of NS is commonlyassumed as an adequate flushing volume in IV catheters.However, Guiffant and colleagues found in their in vitro studythat even after a pulsatile flush with 10mL a 100% removalof the proteins was not obtained [11]. In particular viscousproducts are more difficult to remove from the catheter wall.Indeed, a higher risk of early catheter-related infection wasfound when blood products and PN were administratedthrough long-term IV catheters [16]. Based on these findingsa flush volume of 20mL is suggested after infusion of viscousproducts such as blood components, PN, and contrast media.Unfortunately, clinical studieswith different flushing volumesare lacking.

Nursing Research and Practice 3

Table 1: Flushing and locking recommendations.

Flushing recommendations

TechniqueUse a pulsatile flow when flushingUse a flush with 10 × 1mL boluses with a time interval of 0.4 s between 2 bolusesUse SAS and SBS order for the administration of mediation/fluids and blood sampling procedures

Volume Use a 10mL flush for all IV catheters (except for peripheral cannulas, use 5mL)Use a 20mL flush after infusion of viscous products like blood components, parenteral nutrition, and contrast media

Regimen Flush with NS before and after administration of drugs of fluids (SAS)Flush with NS before and after blood sampling (SBS)

Locking recommendations

Technique Use the positive pressure technique when disconnecting a syringeClose clamps and let them closed when not in use

Volume1.0mL for peripheral cannulas1.5mL for midlines, PICCs, nontunnelled CVCs, and small bore tunnelled catheters (≤1mm ID)2.5mL for large bore tunnelled catheters (>1mm ID) and TIVADs (reservoir volume up to 0.6mL, Huber needlevolume not included)

Regimenq8h–q24h for short-term cathetersWeekly in long-term cathetersq6w–q8w in TIVADs

3.3. Flushing Regimen. Flushing the catheter is the mostimportant factor in preventing malfunction by maintainingcatheter patency. The fact that fibrin and other deposits areimpeded in attaching to the intraluminal catheter wall isparamount. Therefore a major recommendation is to flushbefore and after administration of medication, also known asthe SAS acronym. The order of IV injections is as follows: anormal saline flush (S), followed by the administration (A)of drugs or fluids, followed by a normal saline flush (S). Theuse of the similar sequence is even more important for bloodsampling procedures due to the viscous nature of blood: SBS,a normal saline flush (S), followed by the blood sampling(B), followed by a normal saline flush (S). If the procedureends with a heparin (H) lock the acronym is SASH andSBSH.The first NS flush provides a clean intraluminal surfacewhich precludes attachment of drug deposits or fibrin. Theflush at the end of the IV administration or blood sam-pling procedure prevents accumulation by intraluminal drugdeposits or fibrin and a clean surface impedes attachmentfrom microorganisms to the inner wall. A 10mL flushingvolume after blood sampling is appropriate because fibrincontact with the catheter wall is limited to some minutes. Incontrast, after a blood transfusion a flush of 20mL is requiredbecause fibrin might deposit to the catheter wall during aprolonged time. Similarly, accidental blood reflux into thecatheter and infusion line, for example, when a infusion bagis empty, requires a manual flush of at least 10mL of NS.

Flushing recommendations that are based on researchand insights are summarized in Table 1.

4. Locking

The goal of an adequate catheter lock is prevention ofpremature termination of catheter function by maintaining

patency when the catheter is not in use. The optimal locksolution prevents clot formation in the catheter and at thecatheter tip, and also prevents microorganism adhesion andbiofilm formation.

4.1. Locking Technique. As far back as in 1987, Shearer sug-gested using the positive pressure technique to prevent back-flow of blood into the catheter. This technique was definedas withdrawing the syringe from the injection site whilestill exerting pressure on the syringe plunger when injectingthe last 0.5mL [17]. Alternatively, this could be preventedby clamping the catheter while injecting the last 0.5mL.Nowadays, technologies may replace this manual positivepressure technique such as specially designed syringes witha plunger rod design (e.g., BD PosiFlush prefilled salinesyringe), neutral or positive displacement connectors, orvalves integrated in catheters (e.g., Groshong catheter, C.R.Bard).

Although the idea of preventing blood influx at thecatheter tip by the positive pressure technique is reasonable,some issues arise. This technique prevents only blood influxat the moment of locking of the catheter. Once the syringeis removed, other effects might influence the internal volumesuch as the clamp thatmight be opened and closed or externalcatheter parts that might be pinched. This phenomenoncauses a push out of locking solution and once the pressureof the pinching/clamping is lifted, the same volume thathas been pushed out will create a backflow of blood at thecatheter tip by negative pressure. From in vitro studies weknow that this pinching also occurs with arm movements inlong catheters inserted in an arm vein. Abduction of the armwill create a larger catheter volume and generates influx atthe catheter tip. On the contrary, adduction of the arm willresult in a smaller catheter volume and a displacement of


Table 2: Internal volume of single lumen venous catheters in mL.

Catheter length (cm) Internal diameter (mm)0.5 0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6

10 0.02 0.03 0.04 0.05 0.06 0.08 0.09 0.11 0.13 0.15 0.18 0.2015 0.03 0.04 0.06 0.08 0.10 0.12 0.13 0.17 0.20 0.23 0.26 0.3020 0.04 0.06 0.08 0.10 0.13 0.16 0.17 0.23 0.27 0.31 0.35 0.4025 0.05 0.07 0.10 0.13 0.16 0.20 0.22 0.28 0.33 0.38 0.44 0.5030 0.06 0.08 0.12 0.15 0.19 0.24 0.26 0.34 0.40 0.46 0.53 0.6035 0.07 0.10 0.13 0.18 0.22 0.27 0.30 0.40 0.46 0.54 0.62 0.7040 0.08 0.11 0.15 0.20 0.25 0.31 0.35 0.45 0.53 0.62 0.71 0.8045 0.09 0.13 0.17 0.23 0.29 0.35 0.39 0.51 0.60 0.69 0.79 0.9050 0.10 0.14 0.19 0.25 0.32 0.39 0.43 0.57 0.66 0.77 0.88 1.0055 0.11 0.16 0.21 0.28 0.35 0.43 0.47 0.62 0.73 0.85 0.97 1.1160 0.12 0.17 0.23 0.30 0.38 0.47 0.52 0.68 0.80 0.92 1.06 1.2165 0.13 0.18 0.25 0.33 0.41 0.51 0.56 0.73 0.86 1.00 1.15 1.3170 0.14 0.20 0.27 0.35 0.45 0.55 0.60 0.79 0.93 1.08 1.24 1.4175 0.15 0.21 0.29 0.38 0.48 0.59 0.65 0.85 0.99 1.15 1.32 1.5180 0.16 0.23 0.31 0.40 0.51 0.63 0.69 0.90 1.06 1.23 1.41 1.6185 0.17 0.24 0.33 0.43 0.54 0.67 0.73 0.96 1.13 1.31 1.50 1.7190 0.18 0.25 0.35 0.45 0.57 0.71 0.78 1.02 1.19 1.38 1.59 1.81

the locking volume. Therefore the authors suggest choosingcatheter material that minimises variation in catheter volume[18]. Iterative movement of locking volume and blood at thecatheter tip is assumed in catheters inserted in the arm orcatheters with an external part that might be pinched. Thisis especially the case in silicone catheters. On the contrary,silicone catheters have a smaller internal/outer diameter ratiowhereby the volume of displacementwill be smaller thanwithpolyurethane catheters. However the clinical implications ofthis phenomenon are lacking; in other words it is unclearif this will lead to a higher rate of catheter occlusion andinfection. The same phenomenon is observed with increasedintrathoracic pressures in cases of, for example, vomiting,coughing, and crying. And, in TIVADs, blood influx willbe present when the Huber needle is removed because theport septum is slightly lifted. This lifting creates a smallinflux of blood at the catheter tip. When the needle leavesthe septum, the septum returns to its normal position and.again, it produces a small positive displacement of lockingsolution [19]. Oncemore, the clinical relevance of these fluidsmovements at the catheter tip is unknown. Moreover, it islikely that the use of a heparin lock before needle removaldoes not have an added value in, for example, a lowerincidence of malfunction problems. Indeed, in a study onlocking TIVADs with NS or with heparin, the Huber needlewas removed without exerting positive pressure to overcomethe blood influx. No more malfunction was found in the NSgroup compared to the heparin group [20]. No studies whichfocused on the malfunction rate with versus without the useof the manual positive pressure technique (without any helpof connectors or valved catheters) have been found.

4.2. Locking Volume. The locking volume must be sufficientto fill the entire catheter. Therefore the volume of add-ons

might be added to the priming volume of the catheter.Internal catheter volumes are relatively small: approximately0.03mL for a peripheral catheter, 0.4mL for a 4 Fr midline,0.6mL for a 4 Fr single lumen nontunnelled central venouscatheter (CVC), 0.7mL for a 4 Fr PICC, 0.7mL, and 1.5mLfor a small and large bore tunnelled catheter (75 cm), respec-tively, and 1.3mL for a TIVAD (large reservoir volume of0.5mL), Huber needle with extension set included.

For trimmed catheters with a circular diameter thecatheter volume might be calculated easily per cm. Themathematic formula of a cylinder is pi × 𝑟2 × ℎ, whereby“𝑟” represents the radius (or half of the diameter) and “ℎ”the height, in our case, the length of the catheter. It is clearfrom this formula that the catheter diameter plays a moredominant role than the catheter length. Table 2 tabulates thevolumes expressed for different internal diameters (ID) ofsingle lumen catheters. A few examples of available cathetersmade of different materials are presented in Table 3. Volumescan be easily used to calculate the approximate volume of atrimmed catheter. Note that a difference in catheter lengthof 10 cm does not result in a substantial extra lock volume:0.02mL for a catheter with an ID of 0.5mm (e.g., a singlelumen Hickman 2.7 Fr) and 0.2mL for a large bore catheterwith an ID of 1.6mm (e.g., a 9.6 Fr single lumen Hickman).For TIVADs the volume of the reservoir should be includedin the total volume. The reservoir volume depends on theTIVAD brand and is commonly ranging between 0.25mLand 0.6mL. The priming volume might be provided by themanufacturers for catheters which may not be trimmed.

The aim of a lock is to fill the catheter entirely. Howeverthe risk of “leakage” of the lock over time has been describedand therefore it is suggested that catheters should be overfilledby approximately 15–20%. However, this extra volume canonly be recommended if the locking solution does not cause


Table 3: Examples of corresponding internal and outer diameters in different types of single lumen catheters.

Internal diameter in mm0.5 0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6

Outer diameter in FrenchPorts, PUR catheters, BBraun 4.5 5 6.5 8.5Ports, Chronoflex CRBard 6 8.5Ports, Silicone catheters, BBraun 6.5 8.5 10PICC, PowerPICC CRBard 4Tunneled catheter, Hickman CRBard 2.7 4.2 6.6 9.6

Table 4: Calculation of recommended locking volumes if lock does not cause adverse effects when systemically injected.

Catheter type Total lock volume in mLMinimum catheter volume in mL

(Approximately internal volume + 20%spillage)

Extra volumea

Peripheral catheters 1.0 0.04 (0.03 + 0.006) 0.9Midline 1.5 0.5 (0.4 + 0.1) 1.0PICC 1.5 0.7 (0.6 + 0.1) 0.8Nontunnelled CVC 1.5 0.7 (0.6 + 0.1) 0.8Small bore tunnelled catheter (≤1mm ID) 1.5 0.8 (0.7 + 0.1) 0.7Large bore tunnelled catheter (>1mm ID) 2.5 1.6 (1.3 + 0.3) 0.9TIVADs (reservoir volume up to 0.6mL) 2.5 1.6 (1.3 + 0.3) 0.9aVolume might be used for add-ons, Huber needle, extension set extra-long catheters, or surplus for the positive pressure technique.

adverse effects when systemically injected [21, 22]. Still a20% extra volume is a limited volume, for example, 0.16mLextra to a locking volume of 0.8mL for the medial lumenof 18G CVC. The total lock volume for this CVC lumenis 1mL. In the literature, the reported locking volumesare significantly larger. However, in current guidelines therecommended volumes are small (twice the internal volume)and controversially also large (5–10mL) [3, 4]. Indeed, a 5–10mL lock volume was found in a survey among ICU nursesregarding flushing practices for short-term CVCs. Nursesreported using heparin volumes of 3mL, 5mL, and 10mL[23]. Consequently, one can state that the injection of a 10mLlocking volume in a short-termCVCwill result in an injectionof 9mL of heparin in the circulation without any residualeffect in the catheter. On the other hand, twice the internalvolume means a locking volume of, for example, 0.06mL fora peripheral catheter, 0.8mL for a CVC, and for 4 Fr PICC,1.4mL.

To avoid confusion and given the available variation incatheter length and diameter, uniform volumes for differentcatheter types are suggested. Table 4 shows the calculation fora more uniform and appropriate catheter lock volume basedon the internal catheter volume (or priming volume) withan added spillage of 20% and an extra volume (≤1mL) foradd-ons or extra-long catheters. Moreover a small volumeof the locking solution will be left over in the syringe aftermanual performance of the positive pressure technique. Sothe extra volumemight be necessary especially for nontrainedhealthcare workers. A uniform lock volume of 1.5mL isrecommended for all small catheters such as peripheral can-nulas, midlines, PICCs, nontunnelled CVCs, and small bore

tunnelled catheters. For large bore tunnelled catheters andTIVADs with a large reservoir, 2.5mL is sufficient. If a strictlyminimum lock volume is recommended, the used volumeshould be limited to the internal volume with, eventually, the20% spillage.

4.3. Locking Regimen. For most low concentration lockingsolutions (e.g., a 100U/mL heparin) the lock solution doesnot need to be aspirated. When the lock is renewed, thenew locking solution may be instilled without aspiration orflushing with NS. Some locking solutions, which might becausing adverse events when injected into the blood circu-lation, must be first aspirated before renewal for example,a 5000U/mL heparin lock. Most guidelines recommenda nonspecified “regular” flush regimen. The optimal timebetween two locking procedures when the catheter is not inuse, is not well studied. Commonly a time period between 8and 24 hours is suggested, although in PICCs and long-termCVCs periods of 1 week or more are also used.

For TIVADs, when accessing the port for the intermittentflushing procedure, it is recommended to flush first witha 10mL NS, before a heparin lock. If the Huber needleis not correctly located in the reservoir, the paravenousadministration of NS, in contrast to heparin, is not harmful.There is also a tendency to prolong the interval betweenintermittent accesses for TIVAD maintenance from monthlyto every 6 to 8 weeks [24, 25] and even longer time periodsare used. More research is needed to provide scientificallyunderpinned answers regarding the best time period to renewa lock.


Locking recommendations that are based on research andinsights are summarized in Table 1.

4.4. Locking Solutions

4.4.1. Heparin. A heparin lock was discussed back in the1970s when IV peripheral cannulas were locked as alternativeto a continuous heparin infusion to keep the cannula patent[26]. In that time, a lock of 1mL heparin (10U/mL) has beenrecommended following each IV injection of medication orevery 8 hours [27]. Since then it also has become clear thatthe risks of heparin have to be taken in account. However,the chance of inducing an iatrogenic haemorrhage followingcatheter flushes is rare. The “heparin flush syndrome” hasbeen described in one case report in which a patient devel-oped postoperative bleeding after multiple blood samplesand cardiac output determinations, resulting in two to threeflushes of 500 to 1000 units per hour during a 12 hours period[28]. Heparin has a half-life of 1-2 hours [29]. Given that shorthalf-life, a catheter lock every 6–8 hours will still be safe forthe patient. Some institutions use a practical guideline to notexceed the 2000 units per 24 hours. A single dose of 900 unitsis approximately 16% of the heparin bolus required to acutelyanticoagulate a 70 kg patient [30].However several other risksare associated with heparin use. The risk of errors in dosageof heparin prompted the labelling of heparin as a “high alert”medication [31–34]. Heparin administration may also lead toheparin-induced thrombocytopenia and hypersensitivity toheparin.These are severe adverse effects of heparin even afterexposure to small quantities of heparin from catheter flushing[35–38]. Moreover an intrinsic risk of heparin is infectionbecause heparin stimulates S. aureus biofilm formation [39].Extrinsic risks are the contamination of multiple dose vialsof heparin-saline solution [40, 41] and the risks associatedwith breaks in the integrity of the IV system. Heparin is alsoassociated with drug incompatibilities. Moreover, guidelinesrecommend the use of heparin in many different waysranging from no heparin but NS as locking solution forperipheral cannulas to heparin at 10 to 100U/mL for centralvenous catheters and TIVADs [3, 4, 42]. For all these reasons,the use of alternative locking solutions should be considered.

4.4.2. Normal Saline. Discontinuation of heparin as lockingsolution seems to be attractive because it eliminates the risksassociated with heparin while it prompt savings in nursingtime, supplies, and costs for the patient and/or the institutionand/or the society. Therefore the hypothesis that there is nostatistical difference for locking a catheter with heparin orNS has been investigated many times in different types ofcatheters. A literature review was conducted to investigatelevel I-II evidence [43] relating to the benefits of interventionson the effectiveness of NS versus heparin as a locking solutionin the prevention ofmalfunction.The results are summarizedfor the different catheter types in Table 5.

In peripheral cannulas, evidence was found for the dis-continuation of the use of heparin locks in twometa-analysesin the early nineties. In these meta-analyses, studies withdifferent heparin concentrations, ranging from 2.5U/mLto 100U/mL, are included [44, 45]. In a more recent

meta-analysis, the evidence was confirmed that there wasno statistically significant difference in duration of patencyor clotting between NS versus a low concentration of hep-arin (10U/mL) as a locking solution. However, the analysisshowed a higher risk of clotting when locking with NSversus with a high concentration of heparin (100U/mL) [46].Since then, 5 randomised controlled trials (RCTs) have beenpublished with controversial results in a wide variation insettings, populations, and variables [47–52]. For midlinesno studies which investigated heparin versus NS as lockingsolution were found. In nontunnelled short-term CVCs, onemeta-analysis was found. However, it was impossible to drawconclusions because different heparin volumes, concentra-tions, and administration routes (IV lock or continuousinfusion or subcutaneously administered) were mixed up inthe analysis [53]. Two RCTs which were published later onreported mixed results [54, 55].

Although the use of neutral and positive displacementconnectors implies no heparin lock requirement, two RCTswith PICCs used the locking solution as dependent variablefor occlusion rather than the connector. In the first study apositive displacement system was combined with the use ofa 10mL NS lock versus 5mL of heparin (100U/mL) [56].In the second study all PICCs were connected to a neutralconnector and patients were randomised to a 10mL of NSlock, 5mL heparin 10U/mL, or 3mL heparin 100U/mL lock[57]. Not surprisingly both studies did not find a statisticallysignificant difference in incidence of occlusion, probably dueto the investigation of a superfluous use of heparin.

In tunnelled catheters, one RCT with a small sample sizefound no difference in nonpatency between a twice daily flushwith 5mL heparin (10U/mL) versus a weekly flush of 9mLNS [58]. In TIVADs one single RCT investigated the patencyrates between TIVADs locked with heparin (100U/mL) andNS. No difference in malfunction rates was found [20].

We can conclude that the use of a heparin lock at aconcentration of 10U/mL does not have any added value overthe use of a NS lock in peripheral cannulas. The availablescientific evidence regarding the efficacy ofNS versus heparin(100U/mL) locking in all types of catheters is weak due to thelimited available methodological rigorous studies.

The use of the positive pressure technique might avoidblood influx at the catheter tip when disconnecting a syringe.This procedure is strongly associated with the knowledge andskills of the healthcare worker. To overcome this problem,supporting technologies such as valves incorporated in thecatheter tip (e.g., Groshong, C.R. Bard) or at the catheterhub (e.g., PASV Technology, Navelyst Medical) have beendeveloped. The integrated valves in PICCs, tunnelled, andport catheters are designed to avoid blood influx because theopening pressure of the valve is higher than the pressuresfound in the venous circulation.The valve opens only duringpositive pressure (injection) or negative pressure (aspiration).Needleless connectors with neutral or positive displacementhave also been developed to prevent blood influx at thecatheter tip. The need for a heparin lock is eliminated withthe use of these valves and connectors. Therefore heparinas locking solution is no longer recommended by the man-ufacturers of these technologies. Few RCTs with a focus


Table 5: RCTs and meta-analyses comparing NS and heparin as locking solution.

Authors, yearEvidence regarding

patency with the use ofNS versus heparin

Concentration, volume ofheparin

Volume of NS Frequency Remarks

Peripheral cannulas

Goode etal. 1991∗ [44]

No statisticallysignificant difference

2.5, 3.3, 10, 16.5, 50, 100,132U/mLVolume NR

NR q8h–q24hSmall number of studies,

variation in methodologicalquality

Peterson andKirchhoff 1991∗[45]

No statisticallysignificant difference 1–5mL, 10 to 100U/mL 1–5mL q8h, q12h,

q24h

Small number of studies, fewpediatric studies, variation in

methodological quality

Randolph et al.1998∗ [46]


10U/mLVolume NR

NR q6h, q8h, q12h Small number of studies

Lower patency rate inNS group

100U/mLVolume NR

NR q6h, q8h Small number of studies

Gyr et al. 1995[47]

Lower patency rate inNS group

10U/mLVolume NR

NR q1h–q8h Pediatric population

LeDuc 1997 [48] No statisticallysignificant difference 3mL 10U/mL 3mL 0.5 h–24 h Pediatric population in

emergency department setting

Niesen et al. 2003[49]

No statisticallysignificant difference 1mL 10U/mL 1mL q12h

Pregnant woman in emergencydepartment setting, limited

statistical powerMok et al. 2007[50]


(1) 1mL 1U/mL(2) 1mL 10U/mL

1mL q6h, q8h Pediatric population

White et al. 2011[51]

No statisticallysignificant difference 1mL 10U/mL 3mL q8h Pediatric population, small

sample sizeBertolino et al.2012 [52]

Lower patency rate inNS group 3mL 100U/mL 3mL q12h Large medical population

Midlines

No evidence availableNontunneled short-term CVCs

Rabe et al. 2002[54]

Lower patency rate inNS group (1) 0.5mL 5000U/mL (2) 0.5mL q48h

(3) Third arm was Vit C200mg/mL, 10mL

0.5mL of locking solution wasinjected after each check forblood return without proper

flushing in between

Schallom et al.2012 [55]


ICU and medical ward, limitedstatistical power, ICU and

medical wardPICCs

Bowers et al. 2008[56]

No statisticallysignificant difference 5mL 100U/mL 10mL q12–24h

A positive displacementconnector was used in the 3

groups, small studyLyons and Phalen2014 [57]


(1) 5mL 10U/mL(2) 3mL 100U/mL

(3) 10mL q12h A neutral connector was used inthe 3 groups, home care setting

Tunneled cathetersSmith et al. 1991[58]


q7d NSSmall sample size, paediatrics,onco-hematology patients

TIVADs

Goossens et al.2013 [20]

No statisticallysignificant difference 3mL 100U/mL 10mL

Heparin atdischarge or

q8wOnco-hematology patients

∗Meta-analysis, NR: not reported.


on catheter patency and locking with heparin versus NSwith the help of these technologies (valves and connectors)are available. Two RCTs compared valved catheters versusnonvalved catheters. A first study fromHoffer and colleaguesfound a statistically significant lower occlusion rate in valvedPICCs locked with NS versus nonvalved PICCs locked withheparin (10mL, 10U/mL) [59]. This was confirmed by a sim-ilar study in TIVADs which found a statistically significantlower incidence of malfunction in valved TIVADs lockedwith NS than in nonvalved TIVADs locked with heparin(10mL, concentration not reported) [60]. Obviously, morelarge scale studies with different types of catheters are neededto generate evidence based knowledge regarding the valueof valved technology in avoiding heparin as a catheter locksolution.

Only one RCT investigated a weekly NS lock with a pos-itive displacement connector versus a twice weekly heparinlock with a standard cap in tunnelled catheters in the paedi-atric onco-hematology population. A lower patency rate wasfound with a NS lock and positive displacement connectorthan a heparin lock 200U/mL (volume not reported) anda standard cap. No difference in total catheter dwell timewas found [61]. In three RCTs the connector or cathetertype (valved or not) was chosen as dependent variable forocclusion and not the type of locking solution. In two of thesestudies, a reduction in potential staff confusion was reportedas reason for the uniform lock regimen with heparin. Inthe first study, patients were randomised to the TIVAD withvalved catheter or TIVAD with nonvalved catheter group.All TIVADs were locked with 5mL of heparin (50U/mL).They found a statistically significant higher occlusion ratein the valved catheter group, despite the heparin use, thanin the nonvalved group [62]. In the second study, patientswith a PICC were assigned to a negative or to one of the twotypes of positive displacement connectors. A heparin lock(3mL of 100U/mL) was used in all types of connectors. Astatistically significant difference between the three groupswas found [63]. Finally, Khalidi and colleagues randomisedpatients with PICCs and midlines to a positive displacementconnector or a standard cap with the use of a heparin lock(concentration and volume not reported). They found nostatistically significant differences between the two groups[64]. Results from these fewRCTswhich investigated catheterpatency combined with valved catheters and needleless con-nectors remain inconclusive.

Finally, three systematic reviews which included all typesof catheters, with or without needleless connectors, valved ornonvalved CVCs are available. Mitchell and colleagues foundweak evidence that locking with a heparin solution versus NSreduces the occlusion rate. Due to methodological concerns,no strong conclusions could be drawn [65]. These findingswere confirmed in two recent systematic reviews [66, 67].

It is obvious that the available studies included differentpatient populations, different catheter types with differentlocking regimens. Moreover different malfunction defini-tions are used and although all of these studies had a strongmethodological design a lot of them ended up with smallsample sizes. All these issuesmight explain whymixed resultsare found. There is an urgent need for further well-designed

studies using uniform terminology and outcomemeasures toinvestigate potential differences inmalfunction rates betweenheparin and NS as locking solution for venous catheters. Tillthen, the choice to abandon heparin as locking solution ismore one of weighing up advantages and disadvantages.

4.5. Other Anticoagulants than Heparin. Lepidurin is an an-ticoagulant which acts through direct thrombin inhibition.Only one small study investigated this locking solution versusheparin in IV catheters. A lepidurin (100 𝜇g) lock was notfound to be superior to a heparin (100U/mL) lock [30].

4.6. Thrombolytic Agents. Urokinase is a thrombolytic agentand therefore effective in the treatment of thrombotic occlu-sion. This fibrinolytic drug may also be used in a moreprophylactic way. Moreover the use of periodic fibrinolytictherapy was also suggested in the prevention of catheter-related infectious complications [68]. Three studies havefocused on the comparison between heparin and urokinase aslocking solution with mixed results. Solomon and colleaguesassigned patients with a tunnelled catheter to a heparin(50U/mL, 5mL) or urokinase (5000U/2mL) lock. Theyfound that the use of twice weekly urokinase lock wasnot more effective in reducing infectious and thromboticcomplications than a heparin lock [69]. Ray and colleaguesrandomised patients with a tunnelled catheter between twicedaily heparin locks (10U/mL) and a weekly urokinase lock(9000U/1.8mL). They found that malfunction rates werestatistically significantly reduced by a urokinase lock com-pared to a heparin lock. This was confirmed by Dillon andcolleagues who assigned paediatric patients with TIVADsand tunnelled catheters to either a heparin (100U/mL) orurokinase (5000U/mL, 1.8mL) lock every twoweeks [70]. NoRCTs were found on the effectiveness of other thrombolyticagents such as recombinant tissue plasminogen activatoror tissue plasminogen activator versus heparin as lockingsolution.

4.7. Antimicrobial and Antiseptic Lock Prophylaxis. Due tothe number of manipulations over time, long-term venouscatheters are prone to breaches in aseptic technique duringthe manipulation of the catheters. The intraluminal sourceof infection is associated with more prolonged dwell times[71]. Moreover microbial colonization will produce a biofilmwhen there is contact with a biomaterial such as the innercatheter wall [72]. An antimicrobial lock might be instilledinto the catheter with a long enough dwell time to preventcolonization andbiofilm formation or to eliminate the biofilm[73]. The antibiotic lock technique was first described in1988 for the treatment of catheter-related sepsis withouta tunnel or entry-site infection in tunnelled catheters inhome PN patients [74]. Currently, antibiotic locks consist ofa highly concentrated antimicrobial, often in combinationwith an anticoagulant (cefazolin, cefotaxime, ceftazidime,ciprofloxacin, daptomycin, gentamicin, linezolid, telavancin,ticarcillin-clavulanic acid, and vancomycin) [75].

A meta-analysis of trials in oncology showed weak scien-tific proof for effectiveness of antibiotic-based lock solutionscompared to heparin in preventing CRBSI. However, in


the included studies, the investigated antibiotic locks wereheterogeneous (vancomycin, amikacin, and ciprofloxacin)and the outcome measurement used was nonspecific (sepsisand noncatheter related sepsis) [76]. Another systematicreview in oncology patients which focused on the preventionof Gram-positive catheter-related infections in long-termCVCs showed a reduction of sepsis. The authors concludedthat further research is needed to identify high risk groupsmost likely to benefit [77]. This is in line with the Centers forDisease Control and Prevention guidelines which state thatantibiotic lock prophylaxis should be reserved for patientswith long term catheters who have a history of multipleCRBSI despite optimal adherence to aseptic technique [78].It is known that the use of an antibiotic lock may increaseantimicrobial resistance and may also increase the risk oftoxicity to the patient resulting from leaking or flushing ofthe lock solution into the systemic circulation. Moreover itwas found that antibiotic treatment, similar to heparin, canstimulate biofilm adherence to the catheter surface [39, 79].Therefore there is an urgent need for alternative nonantibioticlocks and nonheparin anticoagulants.

Nonantibiotic locks or antiseptics kill bacteria throughphysical effects rather than specific biochemical pathwaysand may not induce microbial resistance [80]. Donlan de-scribed different approaches to the control of biofilms onintravascular catheters with chelating agents, ethanol, andtaurolidine [73]. Chelating agents have the potential toremove established biofilm (bacteria and fungi). Sodium cit-rate and ethylenediaminetetraacetic acid (EDTA) are chelat-ing agents. EDTA is used alone or in combinations withantibiotics [80, 81].

Ethanol also has the potential to remove establishedbiofilm (bacteria). A systematic review suggested that aprophylactic ethanol lock decreases the rates of infection andunplanned catheter removal and that ethanol lock treatmentappears efficacious in combination with systemic antibiotics.However the review was based mainly on retrospectivestudies [82]. A recent RCT comparing heparin (50U in 5mL)versus 70% ethanol lock (2 hours dwell time) in hematologypatients with tunnelled catheters failed to show a statisticallysignificant reduction in central-line-associated bloodstreaminfection (CLABSI) rates. However the required number ofincluded patients was not attained and therefore the lackof impact on CLABSI rates might be underestimated [83].The use of ethanol has been associated with adverse events.Mermel and colleagues described an increased incidenceof systemic side effects, breaches in the integrity of thecatheter, and catheter obstruction. Further large scale RCTsto assess the safety and efficacy of ethanol lock solutions andlimiting the maximum concentration of ethanol to 28% inlock solutions are suggested [84, 85]. One newly developedlocking solution has reduced the ethanol concentration in thelocking solution to 20% in combination with 0.01% glyceryltrinitrate and 7% citrate. This lock showed promising resultsin eradicating biofilm in an in vitro test [86].

Taurolidine, a derivative of the amino acid taurine, is anantimicrobial agent showing a broad spectrum of antimi-crobial activity against both bacteria and fungi [87, 88]. Ameta-analysis of 6 small studies in patients with different

catheter types and taurolidine concentrations suggest thattaurolidine as locking solution reduces the CRBSI incidencewithout obvious adverse effects and bacterial resistance [89].Abnormal taste sensations were reported in two studies [90,91].

Some antimicrobial and antisepticlocks are not alwaysconsidered as traditional “locks.” They do not fulfill all con-ditions of the earlier definition that a lock is instilled for theperiod of time when the catheter is not in use. Antimicrobialand antiseptic locks might dwell for a limited time and acommon locking solution, such as heparin, might be utilisedin between.

5. Conclusion

Maintaining patency has always been considered essential forall types of venous catheters. Flushing with NS is importantand probably the most crucial factor in the preventionof malfunction. However, evidence on flushing techniques,volumes, and regimens is lacking.Moreover, also the availablescientific basis for catheter locking with heparin is weak.Hence, clinical studies with a strong methodological designand a focus on flushing and locking in relation to malfunc-tion are urgently needed. Uniform malfunction definitions,terminology, and measurements should be used.

Meanwhile, more standardised flushing and locking vol-umes should be used. Flushing volumes should be at least10mL in order to rinse the catheter sufficiently. Lockingvolumes should be minimal and based on the cathetervolume. A maximum of 1mL lock volume surplus is suitableto safely fill the catheter and any add-ons. For peripheralcannulas, a high flushing and locking volume of the catheteris not needed due to the small internal volume of the catheter.

The prevention of CRBSI due to biofilm formation isan increasingly important issue. For long-term CVCs andespecially in susceptible patients an antimicrobial or antisep-ticlock must be considered.

Conflict of Interests

The author declares that there is no conflict of interestsregarding the publication of this paper.

References

[1] J. L. Baskin, C.-H. Pui, U. Reiss et al., “Management of occlusionand thrombosis associated with long-term indwelling centralvenous catheters,” The Lancet, vol. 374, no. 9684, pp. 159–169,2009.

[2] A. Ferroni, F. Gaudin, G. Guiffant et al., “Pulsative flushing asa strategy to prevent bacterial colonization of vascular accessdevices,”Medical Devices: Evidence and Research, vol. 7, pp. 379–383, 2014.

[3] Infusion Nurses Society, “Infusion nursing standards of prac-tice,” Journal of Infusion Nursing, vol. 34, no. 1, supplement, pp.S1–S110, 2011.

[4] Royal College of Nursing IV Therapy Forum, Standards forInfusion Nursing, Royal College of Nursing IVTherapy Forum,2010.


[5] C. A. Schiffer, P. B. Mangu, J. C. Wade et al., “Central venouscatheter care for the patient with cancer: american Societyof Clinical Oncology clinical practice guideline,” Journal ofClinical Oncology, vol. 31, no. 10, pp. 1357–1370, 2013.

[6] G. A. Goossens, Totally implantable venous access devices: mal-function problems unveiled [Ph.D. dissertation], KU Leuven,Leuven, Belgium, 2011.

[7] D. Macklin, “What’s physics got to do with it? A review of thephysical principles of fluid administration,” Journal of VascularAccess Devices, vol. 4, no. 2, pp. 7–11, 1999.

[8] K. G. Tingey, “A review of silicone and polyurethane materialin IV catheters,” Journal of Vascular Access Devices, vol. 5, no. 3,pp. 14–16, 2000.

[9] L. H. Smith, “Implanted ports, computed tomography, powerinjectors, and catheter rupture,” Clinical Journal of OncologyNursing, vol. 12, no. 5, pp. 809–812, 2008.

[10] J. P. Vigier, J. Merckx, J. Y. Coquin, P. Flaud, and G. Guiffant,“The use of a hydrodynamic bench for experimental simulationof flushing venous catheters: impact on the technique,” RevueEuropeenne de Technologie Biomedicale, vol. 26, no. 2, pp. 147–149, 2005.

[11] G. Guiffant, J. J. Durussel, J. Merckx, P. Flaud, J. P. Vigier, and P.Mousset, “Flushing of intravascular access devices (IVADS)—efficacy of pulsed and continuous infusions,” Journal of VascularAccess, vol. 13, no. 1, pp. 75–78, 2013.

[12] M. C. Douard, E. Clement, G. Arlet et al., “Negative catheter-tipculture and diagnosis of catheter-related bacteremia,”Nutrition,vol. 10, no. 5, pp. 397–404, 1994.

[13] F. Brouns, A. Schuermans, J. Verhaegen, I. De Wever, andM. Stas, “Infection assessment of totally implanted long-termvenous access devices,” Journal of Vascular Access, vol. 7, no. 1,pp. 24–28, 2006.

[14] M. Dalton, N. Pheil, J. Lacy, and J. Dalton, “Does sludge/debrisexist in today’s vascular access ports?” Journal of the Associationfor Vascular Access, vol. 19, no. 1, pp. 23–26, 2014.

[15] M. Dalton, N. Pheil, J. Lacy, and J. Dalton, “The port clearancetest: why it is important to clinicians,” Journal of the Associationfor Vascular Access, vol. 19, no. 1, pp. 42–46, 2014.

[16] N. Penel, J.-C. Neu, S. Clisant, H. Hoppe, P. Devos, and Y.Yazdanpanah, “Risk factors for early catheter-related infectionsin cancer patients,” Cancer, vol. 110, no. 7, pp. 1586–1592, 2007.

[17] J. Shearer, “Normal saline flush versus dilute heparin flush,”National Intravenous Therapy Association, pp. 425–427, 1987.

[18] G. Guiffant, P. Flaud, P. Dantan, C. Dupont, and J. Merckx,“Incidence of the curvature of a catheter on the variations of theinner volume: application to the peripherally central catheters,”ISRN Vascular Medicine, vol. 2012, Article ID 803128, 6 pages,2012.

[19] J. Lapalu, M.-R. Losser, O. Albert et al., “Totally implantableport management: impact of positive pressure during needlewithdrawal on catheter tip occlusion (an experimental study),”Journal of Vascular Access, vol. 11, no. 1, pp. 46–51, 2010.

[20] G. A. Goossens, M. Jerome, C. Janssens et al., “Comparingnormal saline versus diluted heparin to lock non-valved totallyimplantable venous access devices in cancer patients: a ran-domised, non-inferiority, open trial,” Annals of Oncology, vol.24, no. 7, Article ID mdt114, pp. 1892–1899, 2013.

[21] H.-D. Polaschegg and C. Shah, “Overspill of catheter lockingsolution: safety and efficacy aspects,” American Society for Arti-ficial Internal Organs Journal, vol. 49, no. 6, pp. 713–715, 2003.

[22] H.-D. Polaschegg, “Catheter locking solution spillage: theoryand experimental verification,” Blood Purification, vol. 26, no.3, pp. 255–260, 2008.

[23] C. Sona, D. Prentice, and L. Schallom, “National survey ofcentral venous catheter flushing in the intensive care unit,”Critical Care Nurse, vol. 32, no. 1, pp. 12–19, 2012.

[24] U. Kefeli, F. Dane, P. F. Yumuk et al., “Prolonged interval inprophylactic heparin flushing for maintenance of subcutaneousimplanted port care in patients with cancer,” European Journalof Cancer Care, vol. 18, no. 2, pp. 191–194, 2009.

[25] A. Palese, D. Baldassar, A. Rupil et al., “Maintaining patency intotally implantable venous access devices (TIVAD): a time-to-event analysis of different lock irrigation intervals,” EuropeanJournal of Oncology Nursing, vol. 18, no. 1, pp. 66–71, 2014.

[26] E. N. Debb and P. E. DiMattia, “Standardization of heparin lockmaintenance solution,” The New England Journal of Medicine,vol. 294, no. 8, p. 448, 1976.

[27] R. L. Hanson, A. M. Grant, and K. R. Majors, “Heparin lockmaintenance with ten units of sodium heparin in one milliliterof normal saline solution,” Surgery Gynecology and Obstetrics,vol. 142, no. 3, pp. 373–376, 1976.

[28] A. Passannante and B. G. Macik, “The heparin flush syndrome:a cause of iatrogenic hemorrhage,” American Journal of theMedical Sciences, vol. 296, no. 1, pp. 71–73, 1988.

[29] D. A. Garcia, T. P. Baglin, J. I. Weitz, and M. M. Samama,“Parenteral anticoagulants: antithrombotic therapy and preven-tion of thrombosis, 9th ed: american college of chest physiciansevidence-based clinical practice guidelines,” Chest, vol. 141, no.2, supplement, pp. e24S–e43S, 2012.

[30] M. K. Horne III, D. J. McCloskey, K. Calis, R. Wesley, R.Childs, and C. Kasten-Sportes, “Use of heparin versus lepirudinflushes to prevent withdrawal occlusion of central venous accessdevices,” Pharmacotherapy, vol. 26, no. 9 I, pp. 1262–1267, 2006.

[31] B. Toft, “The dangers of heparin flushes,” Postgraduate MedicalJournal, vol. 86, no. 1012, pp. 65–66, 2010.

[32] A. Kambal, M. Najem, and T. S. Hussain, “Multi-dosage vials,potential for overdose,”British Journal of Clinical Pharmacology,vol. 58, no. 6, p. 677, 2004.

[33] S. Misra, T. Koshy, and P. Sinha, “Identical drug packaging:heparin and midazolam-yet another instance of similar drugpackaging,” Annals of Cardiac Anaesthesia, vol. 12, no. 1, pp. 88–89, 2009.

[34] C. S. Niccolai, R. W. Hicks, L. Oertel, and J. L. Francis, “Unfrac-tionated heparin: focus on a high-alert drug,”Pharmacotherapy,vol. 24, no. 8, part 2, pp. 146S–155S, 2004.

[35] M. A. Refaai, T. E. Warkentin, M. Axelson, K. Matevosyan, andR. Sarode, “Delayed-onset heparin-induced thrombocytopenia,venous thromboembolism, and cerebral venous thrombosis: aconsequence of heparin ‘flushes’,”Thrombosis and Haemostasis,vol. 98, no. 5, pp. 1139–1140, 2007.

[36] I. Garajova, G. Nepoti, M. Paragona, G. Brandi, and G. Biasco,“Port-a-Cath-related complications in 252 patients with solidtissue tumours and the first report of heparin-induced delayedhypersensitivity after Port-a-Cath heparinisation,” EuropeanJournal of Cancer Care, vol. 22, no. 1, pp. 125–132, 2013.

[37] A. A. Muslimani, B. Ricaurte, and H. A. Daw, “Immuneheparin-induced thrombocytopenia resulting from precedingexposure to heparin catheter flushes,” The American Journal ofHematology, vol. 82, no. 7, pp. 652–655, 2007.

[38] F. Lovecchio, “Heparin-induced thrombocytopenia,” ClinicalToxicology, vol. 52, no. 6, pp. 579–583, 2014.


[39] R.M.Q. Shanks, J. L. Sargent, R.M.Martinez,M. L. Graber, andG.A.O’Toole, “Catheter lock solutions influence staphylococcalbiofilm formation on abiotic surfaces,” Nephrology DialysisTransplantation, vol. 21, no. 8, pp. 2247–2255, 2006.

[40] D. Liu, L.-P. Zhang, S.-F. Huang et al., “Outbreak of Serratiamarcescens infection due to contamination ofmultiple-dose vialof heparin-saline solution used to flush deep venous cathetersor peripheral trocars,” Journal of Hospital Infection, vol. 77, no.2, pp. 175–176, 2011.

[41] M. B. S. Dias, A. B. Habert, V. Borrasca et al., “Salvage oflong-term central venous catheters during an outbreak of Pseu-domonas putida and Stenotrophomonas maltophilia infectionsassociated with contaminated heparin catheter-lock solution,”Infection Control and Hospital Epidemiology, vol. 29, no. 2, pp.125–130, 2008.

[42] Registered Nurses’ Association of Ontario, “Care and Main-tenance to Reduce Vascular Access Complications, Guidelinesupplement,” 2008.

[43] OCEBMLevels of EvidenceWorkingGroup andOxford Centrefor Evidence-Based Medicine, The Oxford 2011 Levels of Evi-dence, OCEBM Levels of Evidence Working Group, OxfordCentre for Evidence-Based Medicine, 2014.

[44] C. J. Goode, M. Titler, B. Rakel et al., “A meta-analysis of effectsof heparin flush and saline flush: quality and cost implications,”Nursing Research, vol. 40, no. 6, pp. 324–330, 1991.

[45] F. Y. Peterson and K. T. Kirchhoff, “Analysis of the researchabout heparinized versus nonheparinized intravascular lines,”Heart & Lung: Journal of Critical Care, vol. 20, no. 6, pp. 631–642, 1991.

[46] A. G. Randolph, D. J. Cook, C. A. Gonzales, and M. Andrew,“Benefit of heparin in peripheral venous and arterial catheters:systematic review and meta-analysis of randomised controlledtrials,” British Medical Journal, vol. 316, no. 7136, pp. 969–975,1998.

[47] P. Gyr, T. Burroughs, K. Smith, C. Mahl, S. Pontious, and L.Swerczek, “Double blind comparison of heparin and salineflush solutions in maintenance of peripheral infusion devices,”Pediatric Nursing, vol. 21, no. 4, pp. 383–389, 366, 1995.

[48] K. LeDuc, “Efficacy of normal saline solution versus heparinsolution for maintaining patency of peripheral intravenouscatheters in children,” Journal of Emergency Nursing, vol. 23, no.4, pp. 306–309, 1997.

[49] K. M. Niesen, D. Y. Harris, L. S. Parkin, and L. T. Henn, “Theeffects of heparin versus normal saline for maintenance ofperipheral intravenous locks in pregnant women,” Journal ofObstetric, Gynecologic, and Neonatal Nursing, vol. 32, no. 4, pp.503–508, 2003.

[50] E.Mok, T. K. Kwong, andM. F. Chan, “A randomized controlledtrial for maintaining peripheral intravenous lock in children,”International Journal of Nursing Practice, vol. 13, no. 1, pp. 33–45, 2007.

[51] M. L. White, J. Crawley, E. A. Rennie, and L. A. Lewandowski,“Examining the effectiveness of 2 solutions used to flush cappedpediatric peripheral intravenous catheters,” Journal of InfusionNursing, vol. 34, no. 4, pp. 260–270, 2011.

[52] G. Bertolino, A. Pitassi, C. Tinelli et al., “Intermittent flushingwith heparin versus saline for maintenance of peripheral intra-venous catheters in a medical department: a pragmatic cluster-randomized controlled study,” Worldviews on Evidence-BasedNursing, vol. 9, no. 4, pp. 221–226, 2012.

[53] A. G. Randolph, D. J. Cook, C. A. Gonzalez, and M. Andrew,“Benefit of heparin in central venous and pulmonary artery

catheters: a meta-analysis of randomized controlled trials,”Chest, vol. 113, no. 1, pp. 165–171, 1998.

[54] C. Rabe, T. Gramann, X. Sons et al., “Keeping central venouslines open: a prospective comparison of heparin, vitamin C andsodium chloride sealing solutions inmedical patients,” IntensiveCare Medicine, vol. 28, no. 8, pp. 1172–1176, 2002.

[55] M. E. Schallom, D. Prentice, C. Sona, S. T. Micek, and L. P.Skrupky, “Heparin or 0.9% sodium chloride tomaintain centralvenous catheter patency: a randomized trial,” Critical CareMedicine, vol. 40, no. 6, pp. 1820–1826, 2012.

[56] L. Bowers, K. G. Speroni, L. Jones, and M. Atherton, “Com-parison of occlusion rates by flushing solutions for peripherallyinserted central catheters with positive pressure luer-activateddevices,” Journal of Infusion Nursing, vol. 31, no. 1, pp. 22–27,2008.

[57] M. G. Lyons and A. G. Phalen, “A randomized controlledcomparison of flushing protocols in home care patients withperipherally inserted central catheters,” Journal of InfusionNursing, vol. 37, no. 4, pp. 270–281, 2014.

[58] S. Smith, S. Dawson, R. Hennessey, and M. Andrew, “Mainte-nance of the patency of indwelling central venous catheters: isheparin necessary?” The American Journal of Pediatric Hema-tology/Oncology, vol. 13, no. 2, pp. 141–143, 1991.

[59] E. K. Hoffer, J. Borsa, P. Santulli, R. Bloch, and A. B. Fontaine,“Prospective randomized comparison of valved versus non-valved peripherally inserted central vein catheters,” AmericanJournal of Roentgenology, vol. 173, no. 5, pp. 1393–1398, 1999.

[60] J. T. Carlo, J. P. Lamont, T. M. McCarty, S. Livingston, and J.A. Kuhn, “A prospective randomized trial demonstrating valvedimplantable ports have fewer complications and lower overallcost than nonvalved implantable ports,” The American Journalof Surgery, vol. 188, no. 6, pp. 722–727, 2004.

[61] S. Cesaro, G. Tridello,M. Cavaliere et al., “Prospective, random-ized trial of two different modalities of flushing central venouscatheters in pediatric patients with cancer,” Journal of ClinicalOncology, vol. 27, no. 12, pp. 2059–2065, 2009.

[62] R. Biffi, F. de Braud, F. Orsi et al., “A randomized, prospectivetrial of central venous ports connected to standard open-endedor Groshong catheters in adult oncology patients,” Cancer, vol.92, no. 5, pp. 1204–1212, 2001.

[63] D. C. Buehrle, “A prospective, randomized comparison of threeneedleless IV systems used in conjunction with peripherallyinserted central catheters,” Journal of the Association for Vascu-lar Access, vol. 9, no. 1, pp. 35–38, 2004.

[64] N. Khalidi, D. S. Kovacevich, L. F. Papke-O’Donnell, and I.Btaiche, “Impact of the positive pressure valve on vascularaccess device occlusions and bloodstream infections,” Journalof the Association for Vascular Access, vol. 14, no. 2, pp. 84–91,2009.

[65] M. D. Mitchell, B. J. Anderson, K. Williams, and C. A.Umscheid, “Heparin flushing and other interventions to main-tain patency of central venous catheters: a systematic review,”Journal of AdvancedNursing, vol. 65, no. 10, pp. 2007–2021, 2009.

[66] A. Dal Molin, E. Allara, D. Montani et al., “Flushing the centralvenous catheter: is heparin necessary?”The Journal of VascularAccess, vol. 15, no. 4, pp. 241–248, 2014.

[67] E. Lopez-Briz, G. Ruiz, V. J. B. Cabello, S. Bort-Marti, S. R.Carbonell, and A. Burls, “Heparin versus 0.9% sodium chlorideintermittent flushing for prevention of occlusion in centralvenous catheters in adults,”TheCochraneDatabase of SystematicReviews, vol. 10, Article ID CD008462, 2014.


[68] S. Kethireddy and N. Safdar, “Urokinase lock or flush solutionfor prevention of bloodstream infections associatedwith centralvenous catheters for chemotherapy: a meta-analysis of prospec-tive randomized trials,”The Journal of Vascular Access, vol. 9, no.1, pp. 51–57, 2008.

[69] B. Solomon, J. Moore, C. Arthur, and H. M. Prince, “Lackof efficacy of twice-weekly urokinase in the prevention ofcomplications associatedwithHickman catheters: amulticentrerandomised comparison of urokinase versus heparin,” Euro-pean Journal of Cancer, vol. 37, no. 18, pp. 2379–2384, 2001.

[70] P. W. Dillon, G. R. Jones, H. A. Bagnall-Reeb, J. D. Buckley,E. S. Wiener, and G. M. Haase, “Prophylactic urokinase in themanagement of long-term venous access devices in children: aChildren’s Oncology Group study,” Journal of Clinical Oncology,vol. 22, no. 13, pp. 2718–2723, 2004.

[71] L. A.Mermel, “What is the predominant source of intravascularcatheter infections?” Clinical Infectious Diseases, vol. 52, no. 2,pp. 211–212, 2011.

[72] M. Ryder, “Evidence-based practice in the management ofvascular access devices for home parenteral nutrition therapy,”Journal of Parenteral and Enteral Nutrition, vol. 30, no. 1,supplement, pp. S82–S93, 2006.

[73] R. M. Donlan, “Biofilm elimination on intravascular catheters:important considerations for the infectious disease practi-tioner,” Clinical Infectious Diseases, vol. 52, no. 8, pp. 1038–1045,2011.

[74] B. Messing, S. Peitra-Cohen, A. Debure, M. Beliah, and J.-J.Bernier, “Antibiotic-lock technique: a new approach to optimaltherapy for catheter-related sepsis in home-parenteral nutritionpatients,” Journal of Parenteral and Enteral Nutrition, vol. 12, no.2, pp. 185–189, 1988.

[75] P. B. Bookstaver, K. E. E. Rokas, L. B. Norris, J. M. Edwards,and R. J. Sherertz, “Stability and compatibility of antimicrobiallock solutions,” American Journal of Health-System Pharmacy,vol. 70, no. 24, pp. 2185–2198, 2013.

[76] M. Snaterse, W. Ruger, W. J. M. Scholte op Reimer, and C.Lucas, “Antibiotic-based catheter lock solutions for preventionof catheter-related bloodstream infection: a systematic reviewof randomised controlled trials,” Journal of Hospital Infection,vol. 75, no. 1, pp. 1–11, 2010.

[77] M.D. van deWetering, J. B. vanWoense, and T. A. Lawrie, “Pro-phylactic antibiotics for preventing Gram positive infectionsassociated with long-term central venous catheters in oncologypatients,” The Cochrane Database of Systematic Reviews, no. 11,Article ID CD003295, 2013.

[78] N. P. O’Grady, M. Alexander, L. A. Burns et al., “Summary ofrecommendations: guidelines for the Prevention of Intravascu-lar Catheter-related Infections,” Clinical Infectious Diseases, vol.52, no. 9, pp. 1087–1099, 2011.

[79] L. R. Hoffman, D. A. D’Argenio, M. J. MacCoss, Z. Zhang, R.A. Jones, and S. I. Miller, “Aminoglycoside antibiotics inducebacterial biofilm formation,”Nature, vol. 436, no. 7054, pp. 1171–1175, 2005.

[80] K. Sauer, J. Steczko, and S. R. Ash, “Effect of a solution contain-ing citrate/Methylene Blue/parabens on Staphylococcus aureusbacteria and biofilm, and comparison with various heparinsolutions,” Journal of Antimicrobial Chemotherapy, vol. 63, no.5, pp. 937–945, 2009.

[81] I. Raad, J. Rosenblatt, R. Reitzel, Y. Jiang, T. Dvorak, and R.Hachem, “Chelator-based catheter lock solutions in eradicatingorganisms in biofilm,” Antimicrobial Agents and Chemotherapy,vol. 57, no. 1, pp. 586–588, 2013.

[82] M. Tan, J. Lau, andB. J. Guglielmo, “Ethanol locks in the preven-tion and treatment of catheter-related bloodstream infections,”Annals of Pharmacotherapy, vol. 48, no. 5, pp. 607–615, 2014.

[83] L. J. Worth, M. A. Slavin, S. Heath, J. Szer, and A. P. Grigg,“Ethanol versus heparin locks for the prevention of centralvenous catheter-associated bloodstream infections: a random-ized trial in adult haematology patients with Hickman devices,”Journal of Hospital Infection, vol. 88, no. 1, pp. 48–51, 2014.

[84] L. A. Mermel and N. Alang, “Adverse effects associated withethanol catheter lock solutions: a systematic review,” Journal ofAntimicrobial Chemotherapy, vol. 69, no. 10, pp. 2611–2619, 2014.

[85] G. Schilcher, A. Schlagenhauf, D. Schneditz et al., “Ethanolcauses protein precipitation—new safety issues for catheterlocking techniques,” PLoSONE, vol. 8, no. 12, Article ID e84869,2013.

[86] J. Rosenblatt, R. Reitzel, T. Dvorak, Y. Jiang, R. Y.Hachem, and I.I. Raad, “Glyceryl trinitrate complements citrate and ethanol ina novel antimicrobial catheter lock solution to eradicate biofilmorganisms,”Antimicrobial Agents and Chemotherapy, vol. 57, no.8, pp. 3555–3560, 2013.

[87] E. D. Olthof, R. Nijland, A. F. Gulich, and G. J. A. Wanten,“Microbiocidal effects of various taurolidine containing cath-eter lock solutions,” Clinical Nutrition, 2014.

[88] W. H. Traub, B. Leonhard, and D. Bauer, “Taurolidine: in vitroactivity against multiple-antibiotic-resistant, nosocomially sig-nificant clinical isolates of Staphylococcus aureus, Enterococcusfaecium, and diverseEnterobacteriaceae,”Chemotherapy, vol. 39,no. 5, pp. 322–330, 1993.

[89] Y. Liu, A.-Q. Zhang, L. Cao, H.-T. Xia, and J.-J. Ma, “Tau-rolidine lock solutions for the prevention of catheter-relatedbloodstream infections: a systematic review and meta-analysisof randomized controlled trials,”PLoSONE, vol. 8, no. 11, ArticleID e79417, 2013.

[90] M. J. Dumichen, K. Seeger, H. N. Lode et al., “Randomizedcontrolled trial of taurolidine citrate versus heparin as catheterlock solution in paediatric patients with haematological malig-nancies,” Journal of Hospital Infection, vol. 80, no. 4, pp. 304–309, 2012.

[91] M. M. Handrup, J. K. Møller, and H. Schrøder, “Centralvenous catheters and catheter locks in children with cancer:a prospective randomized trial of taurolidine versus heparin,”Pediatric Blood & Cancer, vol. 60, no. 8, pp. 1292–1298, 2013.

Submit your manuscripts athttp://www.hindawi.com

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


Gastroenterology Research and Practice

Breast CancerInternational Journal of


HematologyAdvances in


ScientificaHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

PediatricsInternational Journal of



Advances in

Urology

HepatologyInternational Journal of


InflammationInternational Journal of


The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014


Computational and Mathematical Methods in Medicine


BioMed Research International


Surgery Research and Practice

Current Gerontology& Geriatrics Research

Hindawi Publishing Corporationhttp://www.hindawi.com

Volume 2014


NursingResearch and Practice

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

HypertensionInternational Journal of


Prostate CancerHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


Surgical OncologyInternational Journal of

review article flushing and locking of venous catheters...

Documents